1AWW, 1AWX, 1B55, 1BTK, 1BWN, 1K2P, 1QLY, 2GE9, 2Z0P, 3GEN, 3K54, 3OCS, 3OCT, 3P08, 3PIX, 3PIY, 3PIZ, 3PJ1, 3PJ2, 3PJ3, 4NWM, 4OT5, 4OT6, 4OTF, 4OTQ, 4OTR, 4RFY, 4RFZ, 4RG0, 4YHF, 4Z3V, 4ZLY, 4ZLZ, 5BPY, 5BQ0, 5FBN, 4RX5, 5FBO
695
12229
ENSG00000010671
ENSMUSG00000031264
Q06187
P35991
NM_001287345NM_000061NM_001287344
NM_013482
NP_000052NP_001274273NP_001274274
NP_038510
Bruton's tyrosine kinase (abbreviated Btk or BTK), also known as tyrosine-protein kinase BTK, is a tyrosine kinase that is encoded by the BTK gene in humans. BTK plays a crucial role in B cell development.
BTK contains five different protein interaction domains. These domains include an amino terminal pleckstrin homology (PH) domain, a proline-rich TEC homology (TH) domain, SRC homology (SH) domains SH2 and SH3, as well as a protein kinase domain with tyrosine phosphorylation activity.[5]
Part of the TH domain is folded against the PH domain while the rest is intrinsically disordered.
BTK plays a crucial role in B cell development as it is required for transmitting signals from the pre-B cell receptor that forms after successful immunoglobulin heavy chain rearrangement.[6] It also has a role in mast cell activation through the high-affinity IgE receptor.[7]
Btk contains a PH domain that binds phosphatidylinositol (3,4,5)-trisphosphate (PIP3). PIP3 binding induces Btk to phosphorylate phospholipase C, which in turn hydrolyzes PIP2, a phosphatidylinositol, into two second messengers, inositol triphosphate (IP3) and diacylglycerol (DAG), which then go on to modulate the activity of downstream proteins during B-cell signalling.[8]
Mutations in the BTK gene are implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia); sometimes abbreviated to XLA and selective IgM deficiency.[9] Patients with XLA have normal pre-B cell populations in their bone marrow but these cells fail to mature and enter the circulation. The Btk gene is located on the X chromosome (Xq21.3-q22).[10] At least 400 mutations of the BTK gene have been identified. Of these, at least 212 are considered to be disease-causing mutations.[11]
Approved drugs that inhibit BTK:
Various drugs that inhibit BTK are in clinical trials:[20]
Bruton's tyrosine kinase was discovered in 1993 and is named for Ogden Bruton, who first described XLA in 1952.[10]
Bruton's tyrosine kinase has been shown to interact with:
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